Kinetically-Persistent Carbocations in C-H Insertion Reactions and Biomimetic Cyclization Cascades

C-H插入反应和仿生环化级联中的动力学持久碳阳离子

• 批准号: 10213783
• 负责人: Hosea Martin Nelson
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2021-07-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10213783
• 关键词: Address; Benign; Biological; Biomimetics; Boron; Carbon; Catalysis; Chemicals; Chemistry; Communities; Coupling; Cyclization; Development; Drug Compounding; Event; Goals; Inorganic Chemistry; Kinetics; Medicine; Methodology; Methods; Mission; Organism; Pharmaceutical Preparations; Planet Earth; Process; Public Health; Reaction; Research; Research Activity; Salts; Silicon; Societies; Terpenes; Theoretical Studies; Transition Elements; United States National Institutes of Health; catalyst; chemical reaction; chemical synthesis; improved; innovation; novel; nucleophilic substitution; practical application; technology development; therapeutic development; tool

Project Summary Nearly all bioactive compounds, whether drug or tool molecule, are built upon frameworks composed of carbon-to-carbon (C–C) bonds. This is evidenced by extensive efforts from the synthetic community aimed at expanding the scope, efficiency, and selectivity of established C–C bond forming reactions. Many of the most commonly employed methods, such as transition metal-catalyzed cross-coupling or nucleophilic substitution reactions, rely on the multi-step conversion of simple building blocks into reactions partners that are appropriately functionalized to partake in C–C bond forming events. Furthermore, many of the transition metal catalysts that are used in these processes are expensive, toxic, and unsustainable due to their low natural abundance. While these existing C–C bond forming processes are powerful, new methods that address the aforementioned shortcomings would facilitate the development of therapeutic compounds. The long-term goal of the proposed research activities is to address this challenge at the fundamental level through the development of novel C–C bond forming reactions. This proposal outlines the first step in achieving this goal through the development of new electrophilic reactions that feature Earth-abundant and biologically benign catalysts. Specifically, we describe C–H arylation processes that are catalyzed by silicon/boron salts. Moreover, we propose new methods for the synthesis of polycyclic terpenes catalyzed by silicon/boron salts. The proposed research is innovative because it describes approaches to C–C bond formation that challenge dogmas in the methodology field. It is innovative because it leverages the tools and concepts of several field of chemistry (reactive intermediate chemistry, total synthesis and fundamental inorganic chemistry) into the development of practical organic transformations. The described studies are significant because they disclose several new strategies to form C–C bonds that are premised on new concepts in catalysis. These concepts will spur diverse and innovative practical applications, and inspire theoretical study. Ultimately the research proposed in this document will contribute to medicine through chemical synthesis and to society through an improved understanding of fundamental chemical reactivity.

项目概要 几乎所有生物活性化合物，无论是药物还是工具分子，都是建立在由以下组成的框架之上： 碳对碳（C-C）键的合成界的广泛努力证明了这一点。 扩大了已建立的 C-C 键形成反应的范围、效率和选择性。 常用的方法，例如过渡金属催化的交叉偶联或亲核取代 反应，依赖于简单构建块到反应伙伴的多步转换 此外，许多过渡金属被适当地功能化以参与 C-C 键形成事件。 这些过程中使用的催化剂价格昂贵、有毒且不可持续，因为其天然含量低 虽然这些现有的 C-C 键形成过程很强大，但新方法可以解决这个问题。 课题的缺点将促进治疗化合物的开发。 拟议的研究活动的目的是通过 该提案概述了实现这一目标的第一步。 通过开发新的亲电子反应，这些反应具有地球丰富且生物良性的特点 具体来说，我们描述了由硅/硼盐催化的C-H芳基化过程。 此外，我们提出了硅/硼盐催化合成多环萜烯的新方法。 拟议的研究具有创新性，因为它描述了挑战 C-C 键形成的方法 它是方法论领域的教条，因为它利用了多个领域的工具和概念。 化学（反应中间体化学、全合成和基础无机化学） 所描述的研究具有重要意义，因为它们揭示了实际有机转化的发展。 形成 C-C 键的几种新策略以催化新概念为前提。 激发多样化和创新的实际应用，并最终激发理论研究。 本文件中提出的建议将通过化学合成为医学做出贡献，并通过化学合成为社会做出贡献 提高对基本化学反应性的理解。